西安市HBsAg阳性产妇白介素12表达在HBV宫内传播中的影响

Effect of IL-12 Expression in HBsAg Positive Pregnant Women on the Intrauterine Transmission of HBV in Xi’an

目的探讨乙肝病毒表面抗原(HBsAg)阳性产妇外周血白介素12(IL-12)水平在乙型肝炎病毒(HBV)宫内传播中的表达变化。方法以陕西省西北妇女儿童医院分娩的288例HBsAg阳性产妇为病例组,以同时期住院的63例HBsAg阴性健康产妇为对照组进行病例对照研究,采用酶联免疫吸附法(ELISA)法检测孕妇外周血乙型肝炎5项指标、HBV-DNA和细胞因子IL-12水平;对其所生291例新生儿于产后24 h内静脉血进行血清学检测乙肝5项和HBV-DNA水平。结果 HBsAg阳性产妇人群发生HBV宫内显性感染率、HBV宫内隐匿性感染率、HBV宫内传播率分别为7.9%(23/291)、40.9%(119/291)和48.8%(142/291)。①HBsAg阴性组产妇的IL-12水平低于HBsAg阳性产妇组及其各类宫内传播分组(P<0.05),HBV显性感染组产妇的IL-12水平低于HBV宫内未传播组(P=0.009);②HBeAg阳性产妇IL-12水平低于乙肝病毒e抗原(HBeAg)阴性组(P=0.009),宫内未传播组中HBeAg阴性产妇IL-12水平高于HBeAg阳性产妇(P=0.012);③孕期抗病毒治疗、注射乙肝疫苗、妊娠孕周各组及宫内传播各组间差异均无统计学意义(P>0.05);④未注射免疫球蛋白组中宫内传播组IL-12水平低于宫内未传播组(P=0.036);⑤自然破膜产妇组IL-12水平高于人工破膜差异有统计学意义(P=0.036);人工破膜组中宫内传播组IL-12水平低于未传播组(P=0.042);⑥高龄产妇组中HBV宫内传播组的IL-12低于未传播组,差异有统计学意义(P=0.041);⑦多因素分析显示:产妇年龄分组、孕期乙肝疫苗注射、出生孕周是影响宫内传播过程中IL-12水平高低的影响因素(P<0.05)。结论 HBV会刺激产妇免疫系统,注射免疫球蛋白可以提高体内的IL-12水平;HBeAg阳性和高载量HBV DNA会抑制IL-12水平;发生HBV宫内传播尤其是宫内显性感染与孕妇外周血IL-12分泌下降有关,对HBsAg阳性产妇不同感染状态下IL-12浓度进行监测,进行分层管理是防控乙肝宫内传播的新措施。

Objective To investigate and discuss the expression change of interleukin 12(IL-12) level in peripheral blood of HBsAg positive pregnant women in the intrauterine transmission of HBV.Methods From January 2012 to September 2015, 288 cases of HBsAg positive pregnant women and 63 cases of normal women, taken as control group in the epidemiological investigation, were collected at Shaanxi Maternal and Children’s Health Hospital. The peripheral blood of pregnant women were detected in five indices of hepatitis B and cytokine IL-12 level by using enzymelinked immunosorbent(ELISA) method, and HBV DNA level by real-time PCR. And the 291 postpartum venous blood samples collected from their babies born in 24 hours were detected for five indices of hepatitis B and HBV DNA level. Results The incidence of intrauterine dominant infection, occult Infection and intrauterine transmission of HBV in HBsAg positive mothers were 7.9%(23/291), 40.9%(119/291) and 48.8%(142/291). The level of IL-12 in HBsAg negative group was significantly lower than that in HBsAg positive group and all kinds of intrauterine transmission groups(P<0.05),and the level of IL-12 in the pregnant women with HBV dominant infection was significantly lower than that in the pregnant women without intrauterine transmission of HBV(P=0.009). The level of IL-12 in HBeAg positive parturients was significantly lower than that in HBeAg negative parturients(P=0.009), and the level of IL-12 in HBeAg-negative parturients was significantly higher than that in HBeAg-positive parturients in intrauterine nontransmission group(P=0.012). The level of IL-12 showed no significant difference between groups of antiviral therapy, Hepatitis B vaccine, gestational age and intrauterine transmission classification(P>0.05). The level of IL-12 in the intrauterine transmission group was significantly lower than that in the intrauterine non-transmission group(P=0.036) in the uninjected immunoglobulin group.The level of IL-12 in natural rupture group was significantly higher than that in artificial rupture group(P=0.036), and the IL-12 level of HBV intrauterine transmission group was significantly lower than that of healthy babies group(P=0.042) in artificial rupture group. The IL-12 level of HBV intrauterine transmission group in the elderly maternal group was significantly lower than that of the healthy babies group, and the difference was statistically significant(P=0.041). Multiple regression analysis indicated that the maternal age grouping, hepatitis B vaccination during pregnancy and gestational age were the influence factors affecting the level of IL-12 in the process of intrauterine transmission(P<0.05). Conclusion HBV infection during pregnancy stimulates the maternal immune system,and the injection of immunoglobulin increases the IL-12 level. However,HBeAg positive and high-load HBV DNA could inhibit IL-12 level. The study found that the intrauterine transmission of HBV,especially intrauterine dominant infection,was associated with the decreased IL-12 secretion in peripheral blood of pregnant women. Accordingly, monitoring the concentration of IL-12 in HBsAg-positive parturients under different infection conditions and the stratified management would be a new measure to prevent and control intrauterine transmission of hepatitis B.